Even low-androgen triple-negative breast cancer responds to anti-androgen therapy
A University of Colorado Cancer Center study published today in the journal Molecular Cancer Therapeutics shows that only about 1 percent of triple-negative breast cancer cells in a tumor must be “androgen-receptor-positive” to show benefit from anti-androgen therapies. There are no FDA-approved targeted therapies for triple-negative breast cancer. Clinical trials currently underway are showing promising preliminary results of anti-androgen-receptor therapies against triple-negative breast cancers expressing a higher percentage of androgen-receptor-positive cells.
“What we’re showing is that the threshold for benefit from anti-androgen-receptor therapies in triple-negative breast cancer may be far lower than we previously thought. This is an extremely optimistic finding for many people who have been without options for targeted cancer therapy,” says Valerie Barton, the study’s first author and PhD candidate in the lab of CU Cancer Center investigator Jennifer Richer, PhD.
Triple-negative breast cancers are those without known hormone or genetic drivers - specifically, breast cancers that do not drive their growth with the hormones estrogen or progesterone, or with the gene HER2. Without a known driver, there has been no “target” in triple-negative breast cancer to treat with targeted therapies, and the triple-negative subtype has the worst five-year survival rate of any breast cancer. The current study is the most recent in an extremely promising line of work at the CU Cancer Center and elsewhere that aims to prove androgen receptors as an additional driver and target in breast cancer
“We’re getting closer to being able to call some triple-negative breast cancers, androgen-receptor-positive breast cancers. And we may have to start referring to the remaining triple-negative breast cancers that are completely without androgen receptors as quadruple-negative breast cancers,” Barton says.
Did You Know…
Black women are twice as likely as white women to develop tumors referred to as being “triple negative.” This is a highly aggressive form of cancer which affects one third of black women who are diagnosed with breast cancer. It is highly aggressive because the targeted therapies currently used to treat the other forms of breast cancer are not as effective in treating triple negative breast cancer.
Within all age categories and all stages of the disease, black women are more likely to die of breast cancer than women of other races.
A growing body of evidence suggests that breast cancer is different biologically in black women.
Low-income black women lack access to quality and appropriate mammography screening.
Even when fully insured, black women often receive unequal treatment and care.
Each day, breast cancer kills five black women in the United States.
The current study treated triple-negative breast cancer cells with the anti-androgen-receptor drug Enzalutamide, currently FDA approved for use as an anti-androgen against prostate cancer. It has been previously shown that Enzalutamide is active against “luminal” triple-negative breast cancer cells that tend to have abundant androgen receptors. Barton and colleagues tested Enzalutamide against non-luminal triple-negative breast cancer cell lines that have far fewer androgen receptors.
“Even in these cells and in mouse models of tumors with low percentage of androgen receptor positive breast cancer cells, we observed that Enzalutamide was significantly effective at reducing proliferation, growth, migration and invasion of cancer cells,” Barton says.
What is Triple Negative Breast Cancer?
A diagnosis of triple negative breast cancer means that the three most common types of receptors known to fuel most breast cancer growth–estrogen, progesterone, and the HER-2/neu gene– are not present in the cancer tumor. This means that the breast cancer cells have tested negative for hormone epidermal growth factor receptor 2 (HER-2), estrogen receptors (ER), and progesterone receptors (PR). Since the tumor cells lack the necessary receptors, common treatments like hormone therapy and drugs that target estrogen, progesterone, and HER-2 are ineffective. Using chemotherapy to treat triple negative breast cancer is still an effective option. In fact, triple negative breast cancer may respond even better to chemotherapy in the earlier stages than many other forms of cancer.
“Our results suggest that anti-androgen receptor therapy may benefit a larger percentage of triple negative breast cancers than previously thought,” Barton says.
Who is at risk for Triple Negative Breast Cancer?
Triple negative breast cancer occurs in about 10-20% of diagnosed breast cancers and is more likely to affect younger people, African Americans, Hispanics, and/or those with a BRCA1 gene mutation.
WHAT IS THE PROGNOSIS FOR TRIPLE NEGATIVE BREAST CANCER?
Triple negative breast cancer can be more aggressive and difficult to treat. Also, the cancer is more likely to spread and recur. The stage of breast cancer and the grade of the tumor will influence your prognosis.
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Garth Sundem
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University of Colorado Denver
Journal
Molecular Cancer Therapeutics